Genomic landscape and precision therapy in prostate cancer: current status and future directions

Abstract Prostate cancer continues to impose a significant health burden worldwide and in the United States, with rising incidence, persistent mortality rates, and disparities in both incidence and patient outcomes. Advances in genomic profiling have highlighted the remarkable heterogeneity of prostate cancer, revealing frequent alterations in key oncogenes, tumor suppressors, and pathways such as androgen receptor signaling and DNA damage repair that drive disease progression and therapy resistance. These molecular discoveries and their mechanistic validation in laboratory and preclinical models are transforming prostate cancer management, enabling more precise, biomarker-driven treatments and clinical trials. However, challenges, including intra- and inter-tumor genomic diversity, remain formidable barriers to progress. This review provides an overview of the current genomic landscape of prostate cancer and discusses recent advances in precision therapy. We also discuss emerging directions in integrating molecular profiling with personalized patient care, while addressing the roadblocks hampering progress. The discussion highlights the critical need for continued innovation in the development of personalized therapies to improve the clinical outcomes for patients with prostate cancer.